Saturday, April 5, 2008

"Exons, Schmexons"

A summary by PZ Myers of Coyne and Wray's keynote speeches on evodevo. It sounds like it would have been fun to see, particularly the dueling t-shits (one is quoted in the title of this post). I think that Coyne is right that the only real way to know where selected changes occur and what type of mutations they are is to do very detailed follow-up work.

I thought I would give a link to a relatively recent paper by Wray's group looking for positive selection in promoters using the human, chimp and macaque sequences (Haygood et al). Their main point (at least in the coding vs noncoding debate) is that many promoters seem to undergo positive selection compared to exons (especially in interesting categories of genes). The paper looks for positive selection by looking for promoter regions that have significantly more substitutions than nearby intronic regions.

I've not read it in a while so I'll avoid commenting on the technical details. However, a lack of genes with d_N/d_S>1 is not proof that genes do not often experience positive selection, just that d_N/d_S>1 is a pretty crappy measure of positive selection. The problem is that d_N incorporates all of the selection against amino-acid changes plus any weak signal of positive selection. For a gene to meet the d_N/d_S>1 criteria it has to have had a whole bunch of amino-acid changes, if positive selection on a gene often involves just a few amino-acid changes it will not satisfy d_N/d_S>1. Promoter sequences on the other had could be made up of a mixture of near-neutrally evolving regions plus a small number of more constrained regions. A few additional substitutions in the promoter due to positive selection could easily tip the balance to make the promoter be 'rapidly evolving' (i.e. faster than the nearby intron) because the promoter's rate of substitution was not that different from the intronic rate anyway. That's not to say that the promoters found to be rapidly evolving are not interesting, just that the results should not be taken to mean that there is more positive selection on promoters than exons, as this is like comparing apples to oranges.

Haygood R, Fedrigo O, Hanson B, Yokoyama KD, Wray GA.
Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution.
Nat Genet. 2007


dipteran said...

You go, boy!


G said...

Thanks Jerry.